This research project will study the blood-brain barrier transport of selected amino acids, dipeptides and biologically active peptides in the rat. Use of the carotid injection technique will permit assessment of blood-brain barrier transport without concern for peripheral metabolism. Amino acid studies will be directed toward finding the transport systems that carry the sulfur containing amino acid, cysteine, and determining what other amino acids inhibit its transport. The results of our cysteine studies will indicate whether the alanine-serine-cysteine neutral amino acid transport system is present in brain capillaries. The extent and nature of peptide penetration will be investigated using the carotid injection technique and the isolated capillary technique. We will determine which peptides penetrate the blood-brain barrier and what transport system they use. A study of peptide transport systems will include measuring the degree of peptide transport inhibition by other peptides and by other amino acids. Peptides to be studied include dipeptides as well as small biologically active peptides such as tyrotropin-releasing hormone and methionine-enkephalon. The study of peptide penetration is especially relevant to understanding central nervous system activity, based upon the evidence that peptides, such as hypothalamic hormones, enter the brain from the plasma and, in turn, modify neuronal activity.